As many enzymes and cell surface receptors possess handedness, the enantiomers of a racemic pair of compounds may be adsorbed, activated, and/or degraded in different manners. In some instances, two enantiomers of a given racemic drug may have different or even opposite pharmacological activities. This aspect in conjunction with other factors within the pharmaceutical industry have stimulated the need for enantiomerically pure intermediates and bulk optically active compounds. Quick access to reasonable amounts of enantiomerically pure materials to assess their pharmaceutical activity is highly desirable to many pharmaceutical companies. Among the asymmetric technologies developed to analyze and separate optically active compounds, the direct separation of enantiomers by HPLC on enantioselective stationary phases has been a subject of intense investigation. As a result, a wide variety of enantioselective stationary phases have been developed. Although a thorough evaluation of all the current enantioselective columns is impossible, the commonly used ones do seem to have their limitations. It is fair to say that the chiral resolution of racemic materials remains a major challenge. This proposal in intended for the rapid development of more efficient stationary phases for enantioselective chromatography. Specifically, parallel combinatorial libraries are proposed for the development of enantioselective stationary phases. These methods will be applied to develop efficient enantoselective stationary phases for separating racemates of several compounds of pharmaceutical importance.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM063812-01
Application #
6364818
Study Section
Special Emphasis Panel (ZRG1-BECM (01))
Program Officer
Edmonds, Charles G
Project Start
2001-07-01
Project End
2006-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
1
Fiscal Year
2001
Total Cost
$214,007
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Li, Min; Huang, Junmin; Li, Tingyu (2008) Enantiomeric separation of alcohols and amines on a proline chiral stationary phase by gas chromatography. J Chromatogr A 1191:199-204
Zhang, Peng; Polavarapu, Prasad L; Huang, Junmin et al. (2007) Spectroscopic rationalization of the separation abilities of decaproline chiral selector in dichloromethane-isopropanol solvent mixture. Chirality 19:99-105
Huang, Junmin; Chen, Hui; Li, Tingyu (2006) Improvement of proline chiral stationary phases by varying peptide length and linker. J Chromatogr A 1113:109-15
Huang, Junmin; Chen, Hui; Li, Tingyu (2006) Studies of the resolution of racemic 1,1'-bi-2-naphthol with a dipeptide chiral selector identified from a small library. J Chromatogr A 1102:176-83
Huang, Junmin; Chen, Hui; Zhang, Peng et al. (2006) Improvement of proline enantioselective stationary phases by replacing the 9-fluorenylmethoxycarbonyl group. J Chromatogr A 1109:307-11
Norick, Amanda L; Li, Tingyu (2005) Study of the racemization observed in the amide bond forming reaction on silica gel. J Chromatogr Sci 43:526-9
Huang, Junmin; Li, Tingyu (2005) Efficient resolution of racemic 1,1'-bi-2-naphthol with chiral selectors identified from a small library. J Chromatogr A 1062:87-93
Huang, Junmin; Li, Tingyu (2005) Highly efficient chromatographic resolution of alpha,alpha'-dihydroxybiaryls. Org Lett 7:5821-3
Barut, Milos; Podgornik, Ales; Brne, Peter et al. (2005) Convective interaction media short monolithic columns: enabling chromatographic supports for the separation and purification of large biomolecules. J Sep Sci 28:1876-92
Huang, Junmin; Zhang, Peng; Chen, Hui et al. (2005) Preparation and evaluation of proline-based chiral columns. Anal Chem 77:3301-8

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